1. Neuroscience

Precise excitation-inhibition balance controls gain and timing in the hippocampus

  1. Aanchal Bhatia
  2. Sahil Moza
  3. Upinder Singh Bhalla  Is a corresponding author
  1. Tata Institute of Fundamental Research, India
https://doi.org/10.7554/eLife.43415
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  1. Aanchal Bhatia
  2. Sahil Moza
  3. Upinder Singh Bhalla
(2019)
Precise excitation-inhibition balance controls gain and timing in the hippocampus
eLife 8:e43415.
https://doi.org/10.7554/eLife.43415
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Abstract

Excitation-inhibition (EI) balance controls excitability, dynamic range, and input gating in many brain circuits. Subsets of synaptic input can be selected or 'gated' by precise modulation of finely tuned EI balance, but assessing the granularity of EI balance requires combinatorial analysis of excitatory and inhibitory inputs. Using patterned optogenetic stimulation of mouse hippocampal CA3 neurons, we show that hundreds of unique CA3 input combinations recruit excitation and inhibition with a nearly identical ratio, demonstrating precise EI balance at the hippocampus. Crucially, the delay between excitation and inhibition decreases as excitatory input increases from a few synapses to tens of synapses. This creates a dynamic millisecond-range window for postsynaptic excitation, controlling membrane depolarization amplitude and timing via subthreshold divisive normalization. We suggest that this combination of precise EI balance and dynamic EI delays forms a general mechanism for millisecond-range input gating and subthreshold gain control in feedforward networks.

Data availability

All simulation data and code are open source and online, available at https://github.com/sahilm89/linearity. Experimental data is available on Dryad (DOI: https://doi.org/10.5061/dryad.f456k4f) .

The following data sets were generated

Article and author information

Author details

  1. Aanchal Bhatia

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4709-115X

  2. Sahil Moza

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2225-8841

  3. Upinder Singh Bhalla

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    For correspondence
    bhalla@ncbs.res.in
    Competing interests
    Upinder Singh Bhalla, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1722-5188

Funding

University Grants Commission (UGC/ISF No. F 6-18/2014 (IC))

  • Upinder Singh Bhalla

Israel Science Foundation (UGC/ISF No. F 6-18/2014 (IC))

  • Upinder Singh Bhalla

Council of Scientific and Industrial Research (Senior Research Fellowship)

  • Sahil Moza

National Centre for Biological Sciences (Graduate Student Fellowship)

  • Aanchal Bhatia
  • Sahil Moza
  • Upinder Singh Bhalla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Ethics

Animal experimentation: All experimental procedures were approved by the National Centre for Biological Sciences Institutional Animal Ethics Committee (Protocol number USB-19-1/2011), in accordance with the guidelines of the Government of India (animal facility CPCSEA registration number 109/1999/CPCSEA) and equivalent guidelines of the Society for Neuroscience. CA3-cre (C57BL/6-Tg (Grik4-cre) G32-4Stl/J mice, Stock number 006474) were obtained from Jackson Laboratories. The animals were housed in a temperature controlled environment with a 14-h light: 10h dark cycle, with ad libitum food and water.

Version history

  1. Received: November 6, 2018
  2. Accepted: April 10, 2019
  3. Accepted Manuscript published: April 25, 2019 (version 1)
  4. Version of Record published: May 14, 2019 (version 2)
  5. Version of Record updated: June 24, 2021 (version 3)

Copyright

© 2019, Bhatia et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Aanchal Bhatia
  2. Sahil Moza
  3. Upinder Singh Bhalla
(2019)
Precise excitation-inhibition balance controls gain and timing in the hippocampus
eLife 8:e43415.
https://doi.org/10.7554/eLife.43415

Share this article

https://doi.org/10.7554/eLife.43415

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